Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis

B. W.S. Robinson, T. L. McLemore, Ronald Crystal

Research output: Contribution to journalArticle

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Abstract

Gamma interferon (IFNγ) is a potent immune mediator that plays a central role in enhancing cellular immune processes. This study demonstrates that while lung mononuclear cells from normal individuals spontaneously release little or no interferon (<10 U/106 cells per 24 h), those from patients with pulmonary sarcoidosis spontaneously release considerable amounts (65±20 U/106 cells per 24 h. P<0.02 compared to normals). Furthermore, cells from patients with active disease release far more interferon than those from patients with inactive disease (101±36 compared to 24±8 U/106 cells per 24 h, P<0.02). Characterization of this interferon using acid sensitivity, specific antibody inhibition, and target cell specificity criteria demonstrated that it was almost entirely IFNγ. This spontaneous release of IFNγ appeared to be compartmentalized to the lung of these patients in that their blood mononuclear cells spontaneously released little or no IFNγ (P<0.02, compared to sarcoidosis lung mononuclear cells) and no IFNγ was detected in their serum. Both lung T lymphocytes and alveolar macrophages contributed to the spontaneous release of IFNγ by lung mononuclear cells from sarcoid patients; purified preparations of T lymphocytes and alveolar macrophages from these patients spontaneously released similar amounts of IFNγ (56±21 and 32±11 U/106 cells per 24 h, respectively, P>0.3). At least one role for IFNγ in the pathogenesis of sarcoidosis appeared to be related to activation of alveolar macrophages, as alveolar macrophages recovered from patients with active disease spontaneously killed [3H]uridine-labeled tumor cell targets (17.7±4.5% cytotoxicity compared with 2.8±0.9% in normals, P<0.02) and purified IFNγ enhanced the ability of alveolar macrophages from sarcoidosis patients with inactive disease to kill similar targets (P<0.001, compared to alveolar macrophages cultured in medium alone). Treatment of sarcoid patients with corticosteroids, a therapy known to suppress the activity of the disease, caused a marked reduction in the level of spontaneous IFNγ release by lung mononuclear cells compared with untreated patients (P<0.02), which suggests that the effectiveness of corticosteroid therapy in controlling active pulmonary sarcoidosis may, at least in part, be due to suppression of IFNγ release.

Original languageEnglish
Pages (from-to)1488-1495
Number of pages8
JournalJournal of Clinical Investigation
Volume75
Issue number5
DOIs
Publication statusPublished - 1 Jan 1985
Externally publishedYes

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Pulmonary Sarcoidosis
Alveolar Macrophages
Interferons
Interferon-gamma
T-Lymphocytes
Lung
Sarcoidosis
Adrenal Cortex Hormones
Uridine
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

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Gamma interferon is spontaneously released by alveolar macrophages and lung T lymphocytes in patients with pulmonary sarcoidosis. / Robinson, B. W.S.; McLemore, T. L.; Crystal, Ronald.

In: Journal of Clinical Investigation, Vol. 75, No. 5, 01.01.1985, p. 1488-1495.

Research output: Contribution to journalArticle

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abstract = "Gamma interferon (IFNγ) is a potent immune mediator that plays a central role in enhancing cellular immune processes. This study demonstrates that while lung mononuclear cells from normal individuals spontaneously release little or no interferon (<10 U/106 cells per 24 h), those from patients with pulmonary sarcoidosis spontaneously release considerable amounts (65±20 U/106 cells per 24 h. P<0.02 compared to normals). Furthermore, cells from patients with active disease release far more interferon than those from patients with inactive disease (101±36 compared to 24±8 U/106 cells per 24 h, P<0.02). Characterization of this interferon using acid sensitivity, specific antibody inhibition, and target cell specificity criteria demonstrated that it was almost entirely IFNγ. This spontaneous release of IFNγ appeared to be compartmentalized to the lung of these patients in that their blood mononuclear cells spontaneously released little or no IFNγ (P<0.02, compared to sarcoidosis lung mononuclear cells) and no IFNγ was detected in their serum. Both lung T lymphocytes and alveolar macrophages contributed to the spontaneous release of IFNγ by lung mononuclear cells from sarcoid patients; purified preparations of T lymphocytes and alveolar macrophages from these patients spontaneously released similar amounts of IFNγ (56±21 and 32±11 U/106 cells per 24 h, respectively, P>0.3). At least one role for IFNγ in the pathogenesis of sarcoidosis appeared to be related to activation of alveolar macrophages, as alveolar macrophages recovered from patients with active disease spontaneously killed [3H]uridine-labeled tumor cell targets (17.7±4.5{\%} cytotoxicity compared with 2.8±0.9{\%} in normals, P<0.02) and purified IFNγ enhanced the ability of alveolar macrophages from sarcoidosis patients with inactive disease to kill similar targets (P<0.001, compared to alveolar macrophages cultured in medium alone). Treatment of sarcoid patients with corticosteroids, a therapy known to suppress the activity of the disease, caused a marked reduction in the level of spontaneous IFNγ release by lung mononuclear cells compared with untreated patients (P<0.02), which suggests that the effectiveness of corticosteroid therapy in controlling active pulmonary sarcoidosis may, at least in part, be due to suppression of IFNγ release.",
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